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PubMed2007

Does three-dimensional power Doppler ultrasound help in discrimination between benign and malignant ovarian masses?

OBJECTIVES: To determine if tumor vascularity as assessed by three-dimensional (3D) power Doppler ultrasound can be used to discriminate between benign and malignant ovarian tumors, if adding 3D power Doppler ultrasound to gray-scale imaging improves differentiation between benignity and malignancy, and if 3D power Doppler ultrasound adds more to gray-scale ultrasound than does two-dimensional (2D) power Doppler ultrasound. METHODS: One hundred and six women scheduled for surgery because of an ovarian mass were examined with transvaginal gray-scale ultrasound and 2D and 3D power Doppler ultrasound. The color content of the tumor scan was rated subjectively by the ultrasound examiner on a visual analog scale. Vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were calculated in the whole tumor and in a 5-cm(3) sample taken from the most vascularized area of the tumor. Logistic regression analysis was used to build models to predict malignancy. RESULTS: There were 79 benign tumors, six borderline tumors and 21 invasive malignancies. A logistic regression model including only gray-scale ultrasound variables (the size of the largest solid component, wall irregularity, and lesion size) was built to predict malignancy. It had an area under the receiver-operating characteristics (ROC) curve of 0.98, sensitivity of 100%, false positive rate of 10%, and positive likelihood ratio (LR) of 10 when using the mathematically best cut-off value for risk of malignancy (0.12). The diagnostic performance of the 3D flow index with the best diagnostic performance, i.e. VI in a 5-cm(3) sample, was superior to that of the color content of the tumor scan (area under ROC curve 0.92 vs. 0.80, sensitivity 93% vs. 78%, false positive rate 16% vs. 27% using the mathematically best cut-off value). Adding the color content of the tumor scan or FI in a 5-cm(3) sample to the logistic regression model including the three gray-scale variables described above improved diagnostic performance only marginally, an additional two tumors being correctly classified. CONCLUSIONS: Even though 2D and 3D power Doppler ultrasound can be used to discriminate between benign and malignant ovarian tumors, their use adds little to a correct diagnosis of malignancy in an ordinary population of ovarian tumors. Objective quantitation of the color content of the tumor scan using 3D power Doppler ultrasound does not seem to add more to gray-scale imaging than does subjective quantitation by the ultrasound examiner using 2D power Doppler ultrasound.

Diagnosis, Differential↗

PubMed1995

Microtubule changes in hematologic malignant cells treated with paclitaxel and comparison with vincristine cytotoxicity.

Using immunofluorescence microscopy with an anti-alpha tubulin monoclonal antibody, we examined the microtubule changes induced by paclitaxel in pathologic cells from 38 hematologic malignancies, and compared the morphologic and cytotoxic changes with those induced by vincristine in vitro. Malignant cells cultured without paclitaxel or vincristine (controls) showed well-developed microtubules radiating from a microtubule organizing center (MTOC). Malignant cells cultured with paclitaxel showed bundling of microtubules and those cultured with vincristine showed crystal formation of the microtubules. In 28 lymphoid malignancies, the difference in the percentage of cells showing microtubular changes with paclitaxel and vincristine was significant (paired t test) after 2h p < 0.01, after 4h P < 0.05, and after 20 h P < 0.05. As paclitaxel is not in clinical use for the treatment of hematologic malignancies in Japan, no clinical material was available. In 6 out of 9 patients with lymphoid malignancies with a previous history of combined chemotherapy including vincristine, paclitaxel produced microtubular changes in a higher percentage of cells than did vincristine. In 10 myeloid malignancies, the percentages of the cells with microtubular changes induced by paclitaxel was also higher than those induced by vincristine (P < 0.05 in 2 h, p < 0.01 in 4h, and p < 0.05 in 20h). Although the number of studied cases was small, this suggests that paclitaxel is as effective as vincristine in certain hematologic malignancies. As microtubular changes induced by paclitaxel and vincristine are easy to assess, the study of microtubular changes induced in vitro by antimicrotubular agents may prove useful in predicting the chemotherapeutic effect in vivo of these agents.

Adolescent↗

PubMed2002

The significance of serum CA 125 elevation in malignant and nonmalignant diseases.

OBJECTIVES: The aims of the study were to investigate whether an elevated CA 125 level signals malignancies other than ovarian cancer and to find the cause of death for 247 women with elevated values among the 5550 women screened in 1986-1988 in the Stockholm population. METHODS: The Swedish Regional Cancer Registry delivered malignancy diagnoses among the 5550 women screened. The Cause of Death Registry gave the cause of death among the women with elevated CA 125 values. RESULTS: Patients with ovarian cancer were excluded. In 44 women with elevated CA 125 values other malignancies were reported to the Cancer Registry. They represent 18% of the entire group with elevated values. Among the 5297 women with normal CA 125 values 13% developed various malignancies. The difference between incidence of malignant disease in women with elevated values and women with normal values is significant, P = 0.02. Especially during the test-related period, from 1 year before to 1 year after the test, malignancies were detected in 6.9% of the population with elevated values and in only 1.6% with normal values (P = < 0.001). Breast cancer and lung cancer were overrepresented among women with elevated CA 125 values (P = 0.015 and < 0.001, respectively). Of the total 5500 women screened, 358 women died with different diagnoses. Elevated CA 125 values had been noted earlier in 25 women, and of these 20 died of malignant diseases, predominantly ovarian, breast, and lung cancer. CONCLUSIONS: Asymptomatic postmenopausal women with elevated CA 125 levels in ovarian carcinoma screening trials should, if ovarian cancer is excluded, be investigated for possible breast or lung cancer. The findings also suggest that elevated CA 125 level is a risk factor for death from malignant disease.

Breast Neoplasms↗

PubMed1987

Proteases and antiproteases related to the coagulation system in plasma and ascites--an approach to differentiate between malignant and cirrhotic ascites.

The concentrations of several proteases and antiproteases known to be present in ascites were tested in plasma and ascitic fluid with regard to their ability to separate ascites according to malignant or nonmalignant disease. Seventeen patients with proven malignant ascites and 37 with ascites due to liver cirrhosis were included. Activities of plasminogen, alpha 2-antiplasmin, antithrombin-III, and factor V, and the concentration of alpha 1-protease inhibitor were significantly higher in the plasma of patients with malignant ascites than in cirrhotic patients. Fibronectin, plasminogen, alpha 2-macroglobulin, alpha 1-protease inhibitor, antithrombin-III, and albumin revealed higher concentrations or activities in malignant ascites than in cirrhotic ascites. Due to a wide variation of most parameters, only fibronectin, antithrombin III, and alpha 1-protease inhibitor in ascites had a sensitivity and specificity higher than 90% for malignant ascites. When the specific protein/albumin ratio was used, only the accuracy of fibronectin was increased reaching a sensitivity and specificity of 100%. The plasma/ascites gradients of the proteins assessed differed significantly, that of fibronectin being much higher (22 +/- 7) than that of all other proteins. In malignant ascites fibronectin concentration was only correlated with alpha 1-protease inhibitor concentration but not with the concentration or activity of all other proteins, while in cirrhotic ascites most proteins revealed a positive correlation. The determination of the fibronectin concentration or the fibronectin/albumin ratio in ascites can differentiate malignant and nonmalignant ascites. All other proteases and antiproteases assessed are of lesser value for this purpose, although most are significantly increased in ascites and plasma of patients with malignant disorders.

Antithrombin III↗

PubMed1994

Role of fine needle aspiration cytology and endoscopic biopsy in the preoperative assessment of pancreatic and peripancreatic malignancies.

Sixty-seven of 207 patients with pancreatic and peripancreatic malignancies underwent preoperative fine needle aspiration cytology (FNA), and 24 patients underwent intraluminal endoscopic biopsies. All patients had confirmation of the diagnosis of malignancy either at operation, autopsy, or by clinical follow-up. FNA of liver metastases was positive for malignancy in 12 of 12 patients. FNA of the pancreas was performed on 44 patients with pancreatic adenocarcinoma and 11 patients with other pancreatic or peripancreatic malignancies. The diagnosis of cancer was established by FNA in 32 of 44 (72.4%) patients with pancreatic adenocarcinoma and 1 of 11 patients (9.1%) with other pancreatic or peripancreatic malignancies. In the patients with pancreatic adenocarcinoma, 17 of 18 patients (94.4%) who had no operative intervention, 12 of 18 (66.7%) patients who had palliative bypass procedures, and 3 of 8 (37.5%) patients resected had positive FNA. Eighteen of 24 patients (75%) who underwent intraluminal endoscopic biopsies, and 11 of 15 (73.3%) with ampullary carcinoma were positive. We believe that FNA is of limited value in the diagnosis of small resectable tumors of the pancreas as it identified cancer in only 3 of 8 patients in whom it was employed. False negative FNA may delay the diagnosis and treatment of pancreatic malignancies. Patients in whom there is a high index of suspicion of pancreatic or peripancreatic malignancy based on clinical presentation, CT scan, or ERCP assessment do not require preoperative, histologic proof of malignancy prior to pancreaticoduodenectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy, Needle↗

PubMed1997

[Positron emission tomography (PET) in diagnosis and therapy planning of malignant lymphoma].

The management of patients who have malignant lymphomas requires functional methods to differentiate residual soft tissue masses. Positron emission tomography (PET) was performed in patients with histologically proven malignant lymphomas prior to the onset of second-line chemotherapy to examine tumor viability. Twenty patients (68 malignant lesions and 3 benign lesions) with Hodgkin lymphomas (HL) as well as 26 patients (46 malignant lesions and 1 benign lesion) with non-Hodgkin lymphomas (NHL) were studied with fluorine-18-deoxyglucose (FDG). Oxygen-15-labelled water was used in addition in 14 patients with 25 lesions to obtain information on the tissue perfusion. PET with FDG is highly sensitive for the detection of viable tumor tissue, all malignant lesions being correctly classified in this study. We noted no statistically significant difference in FDG metabolism for Hodgkin and non-Hodgkin lymphomas. Even normal-sized lymph-node metastases (< 1 cm) were detected with PET and FDG. The possible limitations are inflammatory processes, which may obscure tumor detection because of the increased FDG uptake, as well as malignant lesions with low FDG uptake as a result of reduced perfusion. Comparison of tumor perfusion and FDG uptake showed a significant nonlinear correlation of r = 0.78 between the two parameters. Two patients with scar tissue and no evidence of malignancy were excluded from blood stem-cell support therapy as a result of the PET study. The data demonstrate that PET is a useful tool for making a diagnosis and deciding on therapy for malignant lymphomas.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

FDG-PET for preoperative differential diagnosis between benign and malignant soft tissue masses.

OBJECTIVE: To evaluate the standardized uptake value (SUV) of [(18)F]2-deoxy-2-fluoro- d-glucose at positron emission tomography (FDG-PET) for preoperative differential diagnosis between benign and malignant soft tissue masses. DESIGN: One hundred and fourteen soft tissue masses (80 benign, 34 malignant) were examined by FDG-PET prior to tissue diagnosis. The SUVs were calculated and compared between benign and malignant lesions and among different histologic subgroups which included three or more cases. RESULTS: There was a statistically significant difference in SUV between benign (1.80+/-1.42 [SD]) and malignant (4.20+/-3.16) soft tissue masses in total (P<0.0001). However, a considerable overlap in SUV was observed between many benign and malignant lesions. Liposarcomas (2.16+/-1.72) and synovial sarcomas (1.60+/-0.43) did not show significantly higher SUV than any benign lesions. Metastases (4.23+/-2.35) showed no statistically significant difference in SUV as compared with schwannomas (1.75+/-0.84), desmoids (2.77+/-1.32), sarcoidosis (3.62+/-1.53), or giant cell tumors of tendon sheath (GCT of TS; 5.06+/-1.63). Even malignant fibrous histiocytomas (5.37+/-1.40) could not be differentiated from sarcoidosis or GCT of TS, based on the SUV. CONCLUSIONS: A large accumulation of FDG can be observed in both benign and malignant histiocytic, fibroblastic, or neurogenic lesions. SUV at conventional FDG-PET is limited to differentiating benign from malignant soft tissue masses, when all kinds of histologic subtypes are included.

Diagnosis, Differential↗

PubMed2001

Power Doppler ultrasonography for the evaluation of skin tumors other than malignant melanoma.

The purpose of this prospective study was to evaluate the value of power Doppler ultrasonography (PDUS) in assessing the vascularity of skin tumors other than malignant melanoma, and to investigate possible diagnostic criteria to help to distinguish malignant from benign tumors preoperatively. Seventy-one patients with the clinical diagnosis of a skin tumor were initially evaluated by ultrasonography. Then PDUS was performed and the presence and type of vascularity (peripheral or mixed) were investigated. Of the 19 benign and 52 malignant lesions, 3 could not be visualized with US. Forty-nine lesions were found to have vascularity (21 peripheral, 28 mixed-type) on PDUS. Of the malignant lesions, 26 showed mixed and 17 showed peripheral-type vascularity; for benign lesions these numbers were 2 and 4 respectively. The presence of vascularity correlated well with pathological behavior (malignant versus benign) (P = 0.00002), width (P = 0.0001), thickness (P = 0.001), dermal disruption (P = 0.0018), and subdermal extension (P = 0.002) of the tumor; however, the type of vascularity correlated only with thickness (P = 0.014). In relation to malignancy, the sensitivity of the presence of vascularity on PDUS was 88% and the specificity was 63%. These values were 93% and 40% respectively, for the mixed type of vascularity when it was accepted as a feature of malignancy. PDUS may help to distinguish malignant from benign skin tumors during preoperative evaluation.

Adolescent↗

PubMed2001

Comparison of interleukin-12 with lung cancer and malignant lymphoma undergoing autologous peripheral blood stem cell transplantation.

PURPOSE: High-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important treatment for solid tumors including lung cancer. METHODS: We measured IL-12 levels in patients with lung cancer undergoing autologous PBSCT in order to elucidate the role of IL-12 in immune response recovery following stem cell transplantation. RESULTS: Compared to IL-12 levels at 1 week after PBSCT for lung cancer patients, those at 3 weeks were significantly increased ( P<0.01). In contrast, serum IL-12 levels in malignant lymphoma patients did not change significantly. There were no significant differences in levels of other cytokines between 1 week and 3 weeks after transplantation in patients with lung cancer. The frequency of helper/inducer T cells was increased in peripheral blood 1 week after transplantation in both lung cancer and malignant lymphoma patients. There was a significant increase in activated T cell numbers following PBSCT. Furthermore, high levels of other activated T cells persisted in the post-PBSCT period in patients with lung cancer and the number of cytotoxic T cells significantly increased. Natural killer (NK) cell numbers also tended to increase, although that of malignant lymphoma was not significant. A strong correlation was observed between serum IL-12 levels and NK cell numbers and interferon-gamma levels in lung cancer not but in malignant lymphoma patients. The analysis of transfused PBSC showed that the numbers of granulocyte/macrophage colony-forming units were similar in lung cancer and malignant lymphoma patients. However, the number of CD34+ cells was significantly higher in lung cancer than in malignant lymphoma patients. All of the CD34+ subpopulations were lower in percentage in patients with lung cancer than in patients with malignant lymphoma. In particular, the CD34+ CD33- subpopulation was significantly lower in percentage in lung cancer patients. CONCLUSION: Our findings suggest that PBSC in lung cancer are potent mediators of anticancer activity and that they might play an immunotherapeutic role against autologous malignant cells.

Adult↗

PubMed2001

Microsatellite instability of colorectal cancer and adenoma in synchronous multiple colorectal cancer patients with associated extracolonic malignancies.

We examined microsatellite instability (MSI) in nonfamilial multiple synchronous colorectal cancer (multiple CC) patients. We divided the patients into two groups, those with and without extracolonic primary malignancies, and compared the frequency of MSI between the two groups. A colectomy was performed in 52 multiple CC patients between 1985 and 1998. Of them, 10 patients had extracolonic malignancies, while the other 42 patients did not. The MSI frequency was higher in the patients with extracolonic malignancies than in those without extracolonic malignancies, although it was not statistically significant (40% vs 19%, P = 0.21). Regarding the lesions, MSI frequency of cancers was higher in the multiple CC with extracolonic malignancies than in those without extracolonic malignancies (33% vs 13%, P = 0.033). From our results, there was statistically no difference in the existence of extracolonic malignancies between the patients with at least one MSI-positive cancer and those patients without any MSI-positive cancers. On the other hand, there was a significant correlation between MSI-positivity and the existence of extracolonic malignancies.

Adenoma↗

PubMed2001

Malignancy in Behçet's disease: a report of 13 cases and a review of the literature.

Behçet's disease (BD) has rarely been reported in association with malignant diseases. In most cases the autoimmune nature of the disease itself or immunosuppressive drug use has been blamed for malignant transformation. We report 13 cases of BD concurrent with neoplastic disease as well as treatment-related morbidities in this particular patient group. Between 1986 and 1999, 400 patients were diagnosed as having BD in Hacettepe University Hospitals. Of these 13 patients, 3.25% developed malignant diseases within a median follow-up time of 9.8 years. Solid tumors were diagnosed in 10 patients and haematological or lymphoid malignancies in three. Surgery was performed in seven patients, whereas radiotherapy was applied in six and chemotherapy in eight. A literature review revealed 27 cases of BD associated with malignancies, mostly lymphoid or haematological. Ten of our cases were solid tumors, and to our knowledge most of these are the first reported cases of specific malignancies concurrent with BD. Treatment-related morbidities were wound infection as surgical morbidity in one patient (1/7) and radiotherapy-related morbidity in three (3/6) patients in a median follow-up time of 2 years. Solid tumors in addition to lymphoid and haematological malignancies are also seen during the course of BD. Radiation therapy may cause severe late toxicities in the presence of BD. Chemotherapy and surgery are fairly safe for the treatment of malignancies in BD patients.

Adult↗

PubMed2005

Malignant transformation of intra-cranial epithelial cysts: systematic article review.

INTRODUCTION: Epidermoid and dermoid cysts are among the most benign intra cranial tumors. Their malignant transformation into squamous cell carcinoma is rare. The authors reviewed the literature. MATERIALS AND METHODS: MEDLINE and SCIENCE DIRECT searches, and examination of the references in the selected articles yielded 74 patients, 52 of whom fulfilled Garcia's criteria and were selected for the study. Survival analyses were performed to determine whether survival differences were of statistical significance, and P < 0.05 was considered as significant. RESULTS: Malignant transformation is characterized by a rapid onset of symptoms, recurrence, leptomeningeal carcinomatosis (LC), and tumor enhancement at Computed Tomography Scan or Magnetic Resonance Imaging (87.8 showed this radiological feature). In this review, the SCCs were classified in five groups: (1) Initial malignant transformation of a benign cyst; (2) malignant transformation from a remnant cyst; (3) malignant transformation of a dermoid and epithelial cyst; (4) malignant transformation with leptomeningeal carcinomatosis; (5) other malignancies arising from benign cysts. The median survival was 9 months. Statistics show that LC was of poor prognosis and radiotherapy, although not statistically significant, seems effective against such lesions, with a median survival of 26 months as opposed to 3 months (P=0.077). CONCLUSION: Although rare, malignant transformation of intracranial epithelial cysts has a poor prognosis and surgery followed by radiotherapy seems to be the best therapeutic modality.

Brain Diseases↗

PubMed2005

Inhibition of cellular proliferation and induction of apoptosis by curcumin in human malignant astrocytoma cell lines.

Nuclear factor (NF)-kappaB is known to control cellular proliferation and apoptosis. In malignant astrocytoma cells, it was reported that NF-kappaB was activated aberrantly and promoted their proliferation. Thus, inhibition of NF-kappaB activity is considered to be a promising therapeutic strategy for malignant astrocytoma. Recently, curcumin, the major constituent of turmeric, was reported to inhibit NF-kappaB activity. In this study, we investigated inhibitory effects of curcumin on NF-kappaB activity and cellular proliferation, and induction of apoptosis by curcumin in human malignant astrocytoma cell lines. Alteration of NF-kappaB activity in NP-2 human malignant astrocytoma cell line after treatment with curcumin was examined using electrophoretic mobility shift assay. Alterations of DNA synthesis and cellular growth in five human malignant astrocytoma cell lines after treatment with curcumin were examined using [(3)H]thymidine incorporation assay and the trypan blue dye exclusion method, respectively. Induction of apoptosis by curcumin in NP-2 and NP-3 human malignant astrocytoma cell lines was examined by DNA-fragmentation analysis and morphological observation. We found that the NF-kappaB activity in NP-2 was significantly reduced by curcumin. The DNA synthesis and the cellular growth were inhibited by curcumin in dose-dependent manner in all the five malignant astrocytoma cell lines. Nuclear condensation and fragmentation, and DNA fragmentation were observed in both NP-2 and NP-3 after the treatment with curcumin. These results indicate that curcumin inhibits the cellular proliferation and induces apoptosis in human malignant astrocytoma cell lines. These results are considered to be resulted from the inhibition of NF-kappaB activity by curcumin.

Antineoplastic Agents↗

PubMed2005

The therapy of infantile malignant brain tumors: current status?

Malignant brain tumors are not uncommon in infants as their occurrence before the age of three represents 20-25% of all malignant brain tumors in childhood [1]. Genetic predisposition to infantile malignant brain tumors are known in Gorlin syndrome for example who present with desmoplastic medulloblastoma in about 5% of the affected patients. In addition, sequelae from tumor and its treatment are more severe at this age [2]. Thus, malignant brain tumors represent a true therapeutic challenge in neuro-oncology. Before the era of modern imaging and modern neurosurgery these malignant brain tumors were misdiagnosed or could not benefit of the surgical procedures as well as older children because of increased risks in this age group. Since the end of the 80s, noninvasive imaging procedures produce accurate diagnosis of brain tumors and improvement in neurosurgery, neuroanesthesia and perioperative intensive care permit safe tumor resections or at least biopsies. Consequently, the pediatric oncologists are more often confronted with very young children who need a complementary treatment. Before the development of specific approaches for this age group, these children received the same kind of treatment than the older children did, but their survival and quality of life were significantly worse. The reasons of these poor results were probably due in part to the fear of late effects induced by radiation therapy, leading to decrease the necessary doses of irradiation which increased treatment failures without avoiding treatment related complications [3]. At the end of the 80s, pilot studies were performed using postoperative chemotherapy in young medulloblastoma patients. Van Eys treated 12 selected children with medulloblastoma with MOPP regimen and without irradiation; 8 of them were reported to be long term survivors [4]. Subsequently, the pediatric oncology cooperative groups studies have designed therapeutic trials for very young children with malignant brain tumors. Different approaches have been explored: * Prolonged postoperative chemotherapy and delayed irradiation as designed in the POG (Pediatric Oncology Group). * Postoperative chemotherapy without irradiation in the SFOP (Société Française d'Oncologie Pédiatrique) and in the GPO (German Pediatric Oncology) studies. * The role of high-dose chemotherapy with autologous stem cells transplantation was explored in different ways: High-dose chemotherapy given in all patients as proposed in the Head Start protocol. High-dose chemotherapy given in relapsing patients as salvage treatment in the French strategy. In the earliest trials, the same therapy was applied to all histological types of malignant brain tumors and whatever the initial extension of the disease. This attitude was justified by the complexity of the classification of all brain tumors that has evolved over the past few decades leading to discrepancy between the diagnosis of different pathologists for a same tumor specimen. Furthermore, it has become increasingly obvious that the biology of brain tumors in very young children is different from that seen in older children. However, in the analysis of these trials an effort was made to give the results for each histological groups, according to the WHO classification and after a central review of the tumor specimens. All these collected data have brought to an increased knowledge of infantile malignant brain tumors in terms of diagnosis, prognostic factors and response to chemotherapy. Furthermore a large effort was made to study long term side effects as endocrinopathies, cognitive deficits, cosmetic alterations and finally quality of life in long term survivors. Prospective study of sequelae can bring information on the impact of the different factors as hydrocephalus, location of the tumor, surgical complications, chemotherapy toxicity and irradiation modalities. With these informations it is now possible to design therapeutic trials devoted to each histological types, adapted to pronostic factors and more accurate treatment to decrease long term sequelae.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Expression of syndecans, a heparan sulfate proteoglycan, in malignant gliomas: participation of nuclear factor-kappaB in upregulation of syndecan-1 expression.

Invasion of tumor cells into the surrounding normal brain tissues is a prominent feature of malignant gliomas. Malignant glioma cells secrete thrombospondin-1 which participates in the motility of glioma cells and binds cell surface heparan sulfate proteoglycan. To clarify the invasion mechanism of tumor cells, expression of the syndecans (syndecan-1, -2, -3, and -4), a major cell surface heparan sulfate proteoglycan family, was analyzed in malignant gliomas. Involvement of nuclear factor-kappaB (NF-kappaB) on syndecan-1 expression was also investigated. Using reverse transcription-PCR, the authors analyzed the expression of syndecan-1, -2, -3, and -4 in 10 malignant glioma cell lines, 2 glioblastoma specimens, and 2 normal brain specimens. All malignant glioma cell lines and glioblastoma specimens expressed all types of syndecan mRNA, except in one glioma cell line that lacked syndecan-3 expression. On the other hand, normal brain specimens expressed syndecan-2, -3, and -4 mRNA, but did not syndecan-1 mRNA. Syndecan-1 protein was localized in the cell surface of all malignant glioma cell lines by flow cytometry. Various levels of active nuclear factor-kappa B (NF-kappaB) was detected in all malignant glioma cell lines using immunoblotting. The expression of active NF-kappaB and syndecan-1 increased in U251 glioma cells after tumor necrosis factor-alpha or interleukin-1beta treatment, which can activate NF-kappaB. The amplification of active NF-kappaB and syndecan-1 by tumor necrosis factor-alpha or interleukin-1beta was suppressed by an inhibitor of NF-kappaB activation (emodin). Emodin also downregulated the expression of syndecan-1 mRNA in U251 cells. These results indicate that malignant glioma cells express all types of syndecans and suggest that NF-kappaB participates in the upregulation of the syndecan-1 expression at the transcriptional level, and increased expression of syndecan-1 could associate with extracellular matrices including thrombospondin-1.

Brain Neoplasms↗

PubMed1990

Histopathology of benign versus malignant sympathoadrenal paragangliomas: clinicopathologic study of 120 cases including unusual histologic features.

The clinical and pathologic features of 120 adrenal and extraadrenal paragangliomas were studied in an attempt to identify features which might predict malignant behavior. Clinical follow-up was obtained in 98 cases (82%); 64 tumors were clinically benign, and 34 were malignant as evidenced by regional or distant metastases and/or extensive local invasion. Thirty-two of the 34 malignant tumors (94%) were functionally active. Features noted more frequently in malignant tumors included male predominance (74%; P2 [two-sided P value] = .002), extraadrenal location (52%; P2 less than .0001), greater tumor weight (mean 383 g versus 73 g for nonmalignant tumors), confluent tumor necrosis, and the presence of vascular invasion and/or extensive local invasion. Intracytoplasmic hyaline globules were seen in 59% and 32% of benign and malignant tumors, respectively (P2 = .001). Logistic regression analysis of 16 nonhistologic and histologic parameters showed four of them to be most predictive of malignancy--extraadrenal location, coarse nodularity of the primary tumor, confluent tumor necrosis, and absence of hyaline globules. Most malignant paragangliomas had two or three of these features (71%), while 89% of benign tumors had only one (or none; P less than .0001). According to the statistical model developed, there was better than a 95% probability that more than 70% of tumors could be classified correctly on the basis of the four factors indicated. Although limitations still exist, results of this study provide some basis for evaluating malignant potential of these tumors.

Adolescent↗

PubMed1994

ME1-antibody labelling of primary bronchogenic tumours and extrapulmonary malignancies.

ME1 is a monoclonal antibody which is generated by the use of a mesothelioma cell line (SPCIII). The antibody has a preferential reaction to antigens on mesothelial and mesothelioma cells. In a prospective study we determined the reactivity in frozen sections from malignant mesotheliomas (two cases, positive controls), lung tumours (115 cases) and other malignant tumours (23 cases). The two malignant mesotheliomas were immunoreactive in most of the tumour cells. The reaction was strong, often with a diffuse staining of the cytoplasm and in some tumour cells there was heavy staining of the cell membrane. Five adenocarcinomas of the lung (9%), one large cell carcinoma (10%) and 18 squamous cell carcinomas of the lung (41%) were positive (defined as tumours containing more than 10% positive tumour cells with a strong reaction). The same was true for seven out of 23 (30%) extrapulmonary malignancies. The overall nosologic specificity of ME1 was 76%. Twenty out of the 26 ME1-positive lung tumours and six out of seven ME1-positive extrapulmonary malignancies were also positive for one or more markers, which is considered characteristic of carcinomas. The six negative lung tumours were squamous cells carcinomas and the negative extrapulmonary tumour was a meningeoma; all of them with a morphology different to malignant mesothelioma. In conclusion, when frozen sections are available, ME1 might be useful in the differential diagnosis of malignant tumours. However, a positive reaction is not specific for malignant mesothelioma.

Adenocarcinoma↗

PubMed1991

Occurrence of other malignancies in 1973 patients with basal cell carcinoma.

To evaluate the possible association of other malignancies with basal cell carcinoma, we reviewed 1973 consecutive patients with basal cell carcinoma. We searched the Swedish Cancer Registry for records reporting malignancies in the study population (1958-1984) and the expected number of malignancies was calculated on the basis of age- and sex-standardized incidence data. In 452 patients with basal cell carcinoma another malignancy was diagnosed. The expected number was 323 (relative risk = 1.4; 95% confidence interval = 1.3 to 1.5). A significant association with basal cell carcinoma was found in four cancer types for men and in three for women. For skin malignancies other than malignant melanoma there was more than a sixfold increased risk for men (relative risk = 6.8; 95% confidence interval = 4.8 to 9.4) and more than a threefold increased risk for women (relative risk = 3.1; 95% confidence interval = 1.4 to 5.9) during the period after the diagnosis of basal cell carcinoma. During the period before the diagnosis of basal cell carcinoma, there were also increased risks (men: relative risk = 5.0; 95% confidence interval = 3.1 to 7.5; women: relative risk = 4.0; 95% confidence interval = 1.9 to 7.4). This was in contrast to the risks of malignant melanoma. Before the diagnosis of basal cell carcinoma there was no significant increased risk of malignant melanoma but after the diagnosis there was more than a sixfold increased risk for men (relative risk = 6.8; 95% confidence interval = 4.8 to 9.4) and more than a fourfold increased risk for women (relative risk = 4.2; 95% confidence interval = 1.5 to 9.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗